White House-Initiated Conference on Epilepsy

White House-Initiated Conference on Epilepsy Emphasizes "No Seizures, No Side Effects"

by Natalie Frazin

NINDS recently coordinated a two-day international scientific conference focused on advances in epilepsy treatment. Initiated by the White House, the conference, "Curing Epilepsy: Focus on the Future," was hailed by participants as an important occasion in epilepsy research, with many envisioning a future when epilepsy not only can be cured (defined as "no seizures, no treatment side effects") but also prevented.

The conference featured presentations and roundtable discussions by more than 30 clinicians and scientists as well as several lay representatives who related their personal experiences with epilepsy. Scientific topics included prospects for interrupting and monitoring epileptogenesis, the processes by which epilepsy develops; genetic strategies for curing epilepsy; and strategies for developing new therapies. More than 500 people attended the conference, which was co-sponsored by the Epilepsy Foundation, the American Epilepsy Society, Citizens United for Research in Epilepsy (CURE), and the National Association of Epilepsy Research Centers.

The conference opened with a videotape of several individuals who shared their experiences with epilepsy and some of its consequences -- a poignant reminder of the human side of epilepsy. This disorder affects an estimated 2.5 million people in the United States and 40 million worldwide. Despite recent advances in treatment, many people with epilepsy still suffer from uncontrolled seizures or from the side effects of treatment. A recent study by the Epilepsy Foundation estimated that the annual financial cost of this disorder is $12.5 billion in the United States alone. Despite clear evidence that epilepsy is a brain disorder, people with epilepsy still suffer from widespread misunderstandings about the condition that can make it difficult for them to obtain education and hold jobs.

"There is no question that epilepsy research is ready for a new infusion and for a dramatic expansion, both in the kinds of research going on and in the quality of that research," said Dr. Gerald Fischbach, director of NINDS, during his introductory address. He praised the co-sponsors for their support of the conference and of biomedical research in general. "One of the really gratifying things about this job is to see private citizens and individuals who . . . get involved in biomedical research."

Highlights of the conference included a videotaped presentation by Hillary Rodham Clinton and a surprise address by U.S. Representative Neil Abercrombie (D., HI), who related how he developed epilepsy more than 30 years ago and urged participants to make themselves known to their representatives in Congress. Former NINDS Deputy Director Dr. Roger Porter also presented an award to Dr. Harvey Kupferberg, who has led the NINDS Antiepileptic Drug Development Program (now the NINDS Epilepsy Therapeutics Research Program) for 18 years and has announced plans to retire in June. Participants in the conference gave Dr. Kupferberg a standing ovation in recognition of his longstanding commitment to epilepsy research.

Scientific presentations at the conference were interspersed with roundtable discussions on strategies emerging from new discoveries, bioethical issues of gene discovery, and the process of moving discoveries from the laboratory to the clinic. For the first time at an NINDS conference, people viewing the lecture via webcast were given the opportunity to submit questions to the speakers by sending email to a special address that was set up for this purpose.

During the plenary talk, "Epilepsy 2000: The Beginning of The End," Dr. Timothy Pedley of Columbia University encouraged scientists to adopt a "new spirit of inquiry in a new millennium," and to expand efforts to engage those outside the mainstream of epilepsy research. He pointed out several advances that are leading to new hope for people with epilepsy, including the molecular genetics revolution, targeted drug development, and brain imaging methods that for the first time allow researchers to use human volunteers as experimental subjects for basic research studies. He also summarized an array of potential new therapies, including stem cell transplants, stimulation of controlled neurogenesis in the brain, and gene replacement. "What is science fiction today may be reality tomorrow," he noted.

Much of the first day was devoted to describing processes of epileptogenesis and how these processes eventually may be interrupted to prevent epilepsy. Dr. Susan Spencer of Yale University School of Medicine opened the first session by describing some of the many factors such as head injury, stroke, and encephalitis that can cause epilepsy. She noted that epilepsy can develop up to 5 years after head injury or other trauma, allowing a significant time window for preventing this disorder. Other presenters described brain monitoring and imaging techniques that can aid in detecting brain changes.

Dr. Francis Collins, director of NHGRI, discussed how advances in the tools of gene research can aid research on epilepsy. These tools include microarrays, or "gene chips" that can analyze the expression of many different genes. Information supplied by these microarrays may lead to advances in diagnosis, prevention, gene therapy, drug therapy, and pharmacogenetics - the science of predicting which drugs are most likely to be successful in treating patients based on expression of different genes. This type of prediction may eventually allow doctors to rapidly identify an effective treatment without serious side effects, instead of the prolonged period of trial and error that is now often required to find an optimal treatment for each patient. Other speakers summarized the current status of genetic research on epilepsy and how genes that affect development can lead to epilepsy.

Dr. Raymond Dingledine of Emory University brought home the need for more innovative drug development research, pointing out that all of the currently available anticonvulsant drugs act on just five molecular targets. He also discussed several promising new targets for drug therapy, including potassium channels and NMDA receptors. Other participants summarized possibilities for refining surgical therapies as well as new strategies such as deep brain stimulation and cell therapy to treat epilepsy. Several presenters also discussed the potential for a device that might be able to detect changes in brain waves that precede a seizure and administer a dose of medication directly to the affected region of the brain. Dr. Daniel Lowenstein, University of California, San Francisco, envisioned an even more advanced device - still entirely hypothetical - that could be implanted in the brain and deliver axon guidance factors or other brain chemicals to draw axons through the chip and alter brain circuitry.

While the focus of the conference was on the scientific presentations, several unique opportunities surrounded the event. These included a special meeting for junior investigators on the night before the conference that introduced a new RFA targeting translational epilepsy research by junior investigators. The conference also included lunchtime sessions that allowed members of the general public to interact with the researchers attending the conference. Finally, a partnership between the Epilepsy Foundation and WebMD provided several online epilepsy discussion panels and an online epilepsy chatroom hosted on the WebMD website during and just after the conference.

Dr. Fischbach described the conference as a wonderful experience that left him with "a great sense of hope and optimism" about prospects for advances in epilepsy research. He also announced the creation of a planning panel that will meet during the next 6 months to develop a 5-year research plan to move toward curing epilepsy. He concluded by calling for industry and academia to find ways to work together to solve the enormous challenge of curing this devastating disorder.

For a list of epilepsy research goals and benchmarks that resulted from this meeting, see Epilepsy Research Web and Benchmarks.